Danil hammoudi.md

Sinoe medical association

THE LEUKEMIAS

-LEUKEMIC CELLS PROLIFERATE PRIMARILY IN :

***BONE MARROW

***LYMPHOIDE TISSUES

-WHERE THEY INTERFERE WITH NORMAL HEMATOPOEISIS AND IMMUNITY.

-ULTIMATELY THEY EMIGRATE INTO THE PERIPHERAL BLOOD AND INFILTRATE OTHER TISSUES..

-CLASSIFICATION :

+++CELL TYPE PRIMARILY INVOLVED : ***MYELOIDE

***LYMPHOID

***CHRONIC

***ACUTE

###ACUTE LYMPHOCYTIC LEUKEMIA [ALL]

###ACUTE MYELOGENOUS LEUKEMIA [AML] OR ACUTE NONLYMPHOCYTIC LEUKEMIA [ANLL]

###CHRONIC LYMPHOCYTIC LEUKEMIA [CLL]

###HAIRY CELL LEUKEMIA

###CHRONIC MYELOGENOUS LEUKEMIA [CML]

ETIOLOGY : UNKNOWN

ACUTE LEUKEMIA OCCURS WITH AN INCREASED FREQUENCY IN A VARIETY OF CONGENITAL DISORDERS INCLUDING :

***DOWN'S

***BLOOM'S

***KLINFELTER'S

***FANCONI'S

***WISKOTT-ALDRICH SYNDROMES

-ATL CAUSED BY HTCL 1 [HUMAN T CELL LEUKEMIA 1] [RETROVIRUS]

-THE INCIDENCE OF BIRTH ACUTE AND CHRONIC LEUKEMIAS IS SOME WHAT HIGHER IN MEN THAN IN WOMEN.

-ALL IS PRIMARILY A DISEASE OF CHILDREN AND YOUNG ADULT.

-AML ALL AGES

-CLL AND HAIRY CELL LEUKEMIA : ELDERLY

[1]

THE MOST COMMON A.L.L VARIANT IS OF B CELL LINEAGE OF NULL VARIETY [ABSCENCE OF FORMATION OF ROSETTES].

PATHOPHYSIOLOGY:

[MYELOBLAST -PROMYELOCYTES]

ACUTE LEUKEMIA IS CHARACTERIZED BY : ***PROLIFERATION OF IMMATURE MYELOID OR LYMPHOID CELLS.

THE MOST PROMINENT CHARACTERISTIC OF NEOPLASTIC CELL IN ACUTE LEUKEMIA IS A DEFECT IN MATURATION BEYOND THE MYELOBLAST OR PROMYELOCYTE LEVEL IN AML, AND THE LYMPHOBLAST LEVEL IN ALL .

AML : ***MYELOBLAST

***PROMYELOCYTE

ALL: ***LYMPHOBLAST.

-LEUKEMIC CELL ACCUMULATE IN THE BONE MARROW DUE :

***BOTH EXCESSIVE PROLIFERATION

***DEFECT TERMINAL MATURATION

IN SOME PATIENTS WITH AML WHO ARE HETEROZYGOUS FOR G6PD ISOENZYMES:

***THE GRANULOCYTES

***MACROPHAGES } ALL CONTAIN THE SIGGLE G6PD ISOENZ PRESENT IN

***ERYTHROCYTES THE LEUKEMIC CELLS

***MEGACARYOCYTES

SUGGESTING THAT THOSE CELLS ARE DERIVED FROM THE MALIGNANT CLONE AND THAT LEUKEMIC TRANSFORMATION INVOLVED A PLEURI POTENT STEM CELLS.

L3 : HAVE A HIGH MITOTIC INDEX AND REPRESENT THE LEUKEMIC FORM OF BURKITT'S LYMPHOMA

ACUTE LEUKEMIAS :

***ACUTE LYMPHOCYTIC LEUKEMIA [ALL]

***ACUTE MYELOGENOUS LEUKEMIA [AML]

DIAG:REQUIRES DEMONSTRATION OF LEUKEMIC CELLS :

+++IN BONE MARROW

+++PERIPHERAL BLOOD

+++EXTRAMEDULLARY TISSUE.

+++BONE MARROW : TIPICALLY HYPERCELLULAR WITH A MONOMORPHIC INFILTRATION OF LEUKEMIC BLASTS AND A MARKED REDUCTION IN NORMAL BONE MARROW ELEMENTS .

IDENTIFICATION OF ALL : -MORPHOLOGY

-IMMUNOLOGIC PHENOTYPE TO STAGE OF LYMPHOID DIFFERENTIATION.

ALL :LEUKEMIC LYMPHOBLAST ARE SMALLER THAN MYELOBLASTS.

THIN RIM OF AGRANULAR CYTOPLASM.

LEUKEMIC LYMPHOBLASTS IN MORE THAN 90% OF PATIENTS WITH A.L.L CONTAIN A NUCLEAR ENZ TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE [Tdt] [RARELY PRESENT IN A.M.L CELLS].

L3 SUBTYPE :Tdt (-)

THIS ENZ IS PRESENT IN IMMATURE T AND B LYMPHOCYTES ABSCENT IN MATURE LYMPHOCYTES.

MOST ALL VARIETY EXPRESS TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE [Tdt] :THIS ENZ IS USEFUL IN DIFFERENTIATING ALL FROM MYELOGENOUS LEUKEMIAS.

-PRESENCE OF AUER RODS [ABDNORMAL PRIMARY GRANULES IN CYTOPLASME] IS DIAG OF A.M.L.

***CLINICAL AND LABORATORY FEATURES:

A.L.L AND AML :

-SYMPTOMS OF ACUTE LEUKEMIA ARE PRESENT FOR LESS THAN 3 MONTHS.

-A PRELEUKEMIC SYNDROME CAN BE IDENTIC IN 25% OF PATIENTS WITH AML ---> IN THESE PATIENTS:

***ANEMIA

***OTHER CYTOPENIA ARE USUALLY PRESENT FOR MONTHS TO YEARS PRECEDING THE DVPLT OF OVER LEUKEMIA.

-A.L.L AND AML MAY PRESENT WITH PANCYTOPENIA WITHOUT CIRCULATING BLASTS ,WITH A NORMAL LEUKOCYTES COUNT ON MARKED LEUKOCYTOSIS

-LEUKOSTASIS DUE TO OCCLUSION OF THE MICROCIRCULATION BY LEUKEMIAS BLASTS CELLS CAN LEAD TO HYPOPERFUSION OF VITAL TISSUES,MOST COMMONLY LUNG AND BRAIN.

-LEUKOSTASIS INCREASE WHEN :***BLASTS CIRCULATING >100 X109/L

> AML THAN A.L.L.

-IN SOME PATIENTS, MEGAKARYOCYTES ARE DERIVED FROM THE LEUKEMIC CLONE AND PRODUCE PLATELETS WITH ABNORMAL FCT.

-SPONTANEOUS BLEEDING INVOLVING THE CNS ,LUNGS,OR OTHER VISCERA MAY ALSO OCCUR.

-INFECTION IS A FREQUENT COMPLICATION OF ACUTE LEUKEMIA.

THE INCIDENCE OF INFECTION IS INVERSELY RELATED TO THE NUMBER OF

CIRCULATING NEUTROPHILS AND BECOMES A MAJOR RISK IN PATIENT WITH GRANULOCYTES COUNT LESS THAN 0.5 X 109 /L

-NEUTROPHILS,DERIVED FROM LEUKEMIC PROGENITORS MAY ALSO FUNCTION ABNORMALLY,FURTHER COMPONISING HOST DEFENSY.

-COMMON SITE OF INFECTION:

***SKIN

***GINGIVA

***PERIRECTAL TISSUES

***LUNG

***URINARY TRACT.

-FREQUENT PATHOGENS:

-/SEPTICEMIA OCCURS WITHOUT AN APPARENCE SOURCE

-/GRAM (-) BACTERIA

-/GRAM (+) " " " "

-/COCCI

-/CANDIDA SPECIES

***HPM AND SPM ARE PRESENT IN 50% TO 75% OF PATIENT [INFILTRATION].

WITH ALL

MINORITY OF PATIENT AML.

***LYMPHOADENOPATHY IS MORE COMMON IN A.L.L THAN A.M.L

AN ANTERIOR MEDIASTINAL MASS IS PRESENT WITH T CELLS IN A.L.L.

TESTICULAR INVOLVEMENT IS PARTICULARLY COMMON WITH T CELL IN A.L.L .

***SOFT TISSUE MASSES OF LEUKOCYTES CELLS " CHLOROMAS" CAN DVLP IN ANY LOCATION.

***THE SERUM LACTIC ACID DEHYDROGENASE [LDH] LEVEL INCREASED.

HYPERURECEMIA ---> DUE TO ACCELERATED TURNOVER OF CELLS WITH INCREASED PURINE RELEASE .

[1]

ACUTE MYELOGENOUS LEUKEMIA:

M1: AML WITHOUT DIFFERENTIATION

M2: AML WITH DIFFERENTIATION

M3: PROMYELOCYTIC LEUKEMIA=ABNORMAL PROMYELOCYTES WITH GIANT GRANULES .

OFTEN ASSOCIATED WITH DIC RELATED TO THROMBOPLASTIC

MYELOMONOCYTIC AND MONOCYTIC LEUKEMIAS : M4-M5=NONERYTHROID CELLS THAT ARE CEREBRIFORM MONOBLASTS.

CHRONIC LYMPHOCYTIC LEUKEMIA CLL

ADULT [50 YEARS OLD]

MATURE LYMPHOCYTOSIS MOST LIKELY HAS CLL

THE CELLS ASSOCIATED WITH CLL ARE MATURE LYMPHOCYTES THAT ACCUNULATE IN THE BODY OVER TIME

MARROW INFILTRATION BY MATURE LYMPHOCYTES ,AN ENLARGED SPLEEN ,AND LYMPHADENOPATHY.

STAGING:

STAGE 0: PERIPHERAL LYMPHOCYTOSIS ONLY.

EXCELLENT PROGNOSTIC .

SURVIVAL 10-12 YEARS

STAGE 1 AND 2: STAGE 1:PERIPHERAL LYMPHOCYTOSIS AND LYMPHOADENOPATHY

STAGE 2 PRESENCE OF SPLENOMEGALY

BOTH STAGE INTERMEDIATE PROGNOSTIC : 4-7 YEARS.

[1]

STAGE 3-4: STAGE 3 : PRESENCE OF ANEMIA

STAGE 4: THROMBOCYTOPENIA

BOTH STAGE SIGNIFY MARROW FAILURE AND HAVE OMINOUS PROGNOSES -18MONTHS

THERAPY : STAGE 1-2 NO TRT

LATE STAGE : ALKYLATING AGENT [CHLORAMBUCIL] WITH OR WITHOUT STEROID .

IRRADIATION

ANTIMETABOLITES =FLUDARABINE.

Y GRANULES IN CYTOPLASME] IS DIAG OF A.M.L.

***CLINICAL AND LABORATORY FEATURES:

A.L.L AND AML :